Parasitic infections generally depend on the ability of the parasite to establish a relationship with the host which, while detrimental to the robust good health of the host, is sufficiently benign to assure the parasite of a sufficiently long-term relationship to continue its own life cycle. An example of such a parasitic relationship is that of heartworm in dogs. Heartworm infection is very common and caused by the nematode, Dirofilaria immitis. Heartworm primarily affects dogs; indeed, in some geographical areas many canines are carriers of this parasite. On the other hand, only a relatively small number of cats in enzootic areas, probably less than 15%, harbor this nematode. It is currently not understood why cats, while susceptible, appear to react to infection differently from their canine counterparts.
Heartworm infection in dogs occurs through passage of the third stage larvae (L3) of D. immitis into the subcutaneous tissue as a result of a mosquito bite. In the subcutaneous tissue, the L3larvae molt into a fourth larval stage (L4) which then migrates toward the thoracic cavity. A subsequent molt to an immature adult occurs and the immature adult gains access to the heart and pulmonary arteries where maturity into adulthood occurs. The L3 remain near the site of infection; L4 migrate through the cutaneous tissue and muscle and do not molt to the fifth stage until 50-70 days after infection. The adult D. immitis are on the order of 12-20 cm (males) and 25-31 cm (females) and produce motile vermiform embryos called microfilariae which are only 0.3 mm long. These embryos traverse capillary beds and circulate in the vascular system. There, the microfilariae are ingested by mosquitoes and continue their life cycle through L3 in the mosquito vector until infection of the host subsequent to the mosquito bite.
As heartworm infection is a recognized problem in dogs, various attempts have been made to prevent or treat this condition. While there have been a number of attempts to prepare vaccines against heartworm infection in dogs, it is clear that this is not a straightforward matter and that the success of a particular vaccine depends on the proper selection of the appropriate antigen. The nature of this antigen is not yet completely established. Because vaccines have not been practical, dogs have been treated with parasiticides after infection.
Cats do not ordinarily harbor heartworm parasites, and when they do, they are likely to die from the infection. It has not been possible to treat infected cats with parasiticides, because while treatment with parasiticides, in particular adulticides, is commonly practiced in dogs, it may be fatal in cats. In general, it is recommended that cats without overt signs of heartworm should not be treated (Hawkins, E. C. Kal Kan Forum (1989) 8:2-7). Cats exhibit severe post-adulticide reactions which often must be treated with oxygen supplementation and corticosteroid administration. Follow up treatment when microfilariae are present using a microfilaricide is also often necessary. Preventatives used in dogs have also been less successful in cats, are not currently approved for use in the United States and are generally not used.
In view of the substantial incidence of harmful heartworm infection in cats, and in view of the great risks associated with post-infection treatment, it would be highly desirable to produce a vaccine which would be protective against heartworm infection in felines, as well as other animals susceptible to but not adapted to a parasite/host relationship with heartworm. Cats, with respect to infection by D. immitis, are a model system of a susceptible host and a parasite which is not adapted to that host. As demonstrated herein, presumably because cats are not adapted to accommodate the heartworm parasite as are dogs, generic stimuli of the immune system are protective against infection. These stimuli include, for example, the administration of cytokines or of immunogens, e.g., proteins or other antigens associated with the various life stages of D. immitis and related nematodes, or mild viral infection.